DJ-1 is one of the rarest gene mutations associated with recessive parkinsonism. Although the function of the DJ-1 protein, which is conserved in aerobic species from E coli to man, is unknown, several observations suggest that it plays a key role in cellular responses to oxidative stress. Several previous studies have suggested that oxidative stress is associated with aging in most aerobic systems. Therefore, our aim in this project is to understand why mutations in such an evolutionarily ancient protein would be associated with age related neurodegeneration of dopaminergic neurons, as seen in Parkinsons disease. Our current work has been to extend our previous observations that DJ-1 expression levels determine cellular responses to oxidative stress. We are characterizing the cellular and molecular phenotypes of cells deficient in DJ-1 using both directed and large scale approaches. We have also begun breeding DJ-1 deficient mice to animals that have accelerated aging phenotypes in an attempt to increase basal phenotypes.